Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019829 (Hodgkin's disease)
 30,247 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To get insight into the failure of the immune system to eradicate Epstein-Barr virus (EBV) harboring Hodgkin and Reed-Sternberg cells (H-RS cells), expressing the latent membrane protein 1 (LMP1), we analyzed major histocompatibility complex (MHC) class I expression on H-RS cells in relation to the presence of activated cytotoxic cells, i.e., granzyme-B-expressing lymphocytes. H-RS cells in EBV+ cases of Hodgkin's disease (HD) were found to express significantly higher levels of MCH class I heavy- and light-chain molecules compared with EBV- HD cases. When low levels of MHc class I expression were found (mainly in EBV- cases), these were not associated with low levels of the transporter protein associated with antigen presentation 1 (TAP-1). The relatively high levels of MHC class I expression in H-RS cells in EBV+ HD cases were accompanied by significantly higher numbers of activated cytotoxic T lymphocytes (CTLs) as shown by the presence of increased numbers of CD8 and granzyme B+ lymphocytes. However, these cells were only sporadically detected in the close vicinity of the H-RS cells. These data suggest that mechanisms other than downregulation of MHC class I or TAP-1 expression on H-RS cells are involved in the failure of the immune system to eradicate EBV harboring H-RS cells. Probably, the function of activated CTLs is locally inhibited by the H-RS cells or by reactive cells in the vicinity of the H-RS cells.
 ...
PMID:Analysis of major histocompatibility complex class I expression on Reed-Sternberg cells in relation to the cytotoxic T-cell response in Epstein-Barr virus-positive and -negative Hodgkin's disease. 861 11

The immunologic attributes of cytokine mobilized peripheral blood stem cell (PSC) products (n = 52) and the resulting reconstitution of the hematopoietic and immunologic system following autologous transplantation were examined in a consecutive population of non-Hodgkin lymphoma (NHL), or solid tumor patients at the University of Nebraska Medical Center. Granulocyte-monocyte colony stimulating factor (GM-CSF)-mobilized PSC products had a high frequency of monocytes (31%) and bands (15%) as compared to normal peripheral blood (PB) cells. The phenotypic analysis of the mobilized PSC product revealed that they had normal levels of CD4+ cells, an increased frequency of CD8+ cells and a corresponding decrease in the CD4+:CD8+ cell ratio as compared to the peripheral blood leukocytes (PBL) of normal individuals. PSC products also had an increase in CD34+ cells as compared to PB. Natural killer (NK) and T cell activity in the PSC products were also lower than that observed in PB. Post-transplantation there was an accelerated reconstitution of NK-cell function in the PB as compared to T cell function (PHA (phytohemagglutinin) mitogenesis) which did not return to normal by day 100 post-transplantation. We also report for the first time high levels of an irradiation resistant suppressor cell activity in the PSC product and in the PB post-transplantation. There was also a concomitant increase in CD4-, CD8-, TCR alpha/beta+ cells (phenotypic homolog of 'natural suppressor' (NS) cells) in the PB post-transplantation. The number of months of prior chemotherapy correlated with PHA response but the NS activity and frequency of CD4-, CD8- and TCR alpha/beta+ cells did not. Further, cytokine mobilization and apheresis appears to contribute to the loss of PHA responsiveness and the increased levels of suppressor cell activity.
 ...
PMID:Immunologic attributes of cytokine mobilized peripheral blood stem cells and recovery following transplantation. 867 41

Tumors of the follicular dendritic cell are uncommon, and most occur as primary lymph node tumors. We report a case of primary follicular dendritic cell tumor of the liver that was initially reported as an inflammatory pseudotumor. The neoplasm recurred as two separate tumor masses 30 months after complete resection of the "hepatic inflammatory pseudotumor." It showed a wide spectrum of morphologic features ranging from areas with fascicles of very bland spindle cells amidst a background population of lymphocytes, reminiscent of inflammatory pseudotumor, to areas of dispersed sheets of highly pleomorphic tumor cells with a relative paucity of reactive inflammatory cells. The diagnosis was confirmed by positive immunohistochemical staining with CD21, CD35, R4/23, and Ki-M4 and by ultrastructural demonstration of convoluted interdigitating cell processes joined by desmosomes. The background lymphocytes were oligoclonal, CD8-positive T cells. In situ hybridization for Epstein-Barr virus (EBV)-encoded RNA was positive in the tumor cells in the original and recurrent tumors. More importantly, the cells showed identical episomal clonal EBV on Southern blot analysis, implying that the initial and recurrent tumors are due to clonal proliferation of EBV-positive neoplastic follicular dendritic cells. The tumor cells expressed latent membrane protein but not EBV-encoded nuclear antigen 2 (EBNA2) or ZEBRA. Such gene expression is very similar to that of Hodgkin's disease and nasopharyngeal carcinoma. The strong expression of latent membrane protein restricted to the tumor cells and the clonality of the EBV suggest that the virus may be involved in the pathogenesis of this tumor and not present merely as a "bystander."
 ...
PMID:Follicular dendritic cell tumor of the liver. Evidence for an Epstein-Barr virus-related clonal proliferation of follicular dendritic cells. 877 85

Lymphocyte predominance Hodgkin's disease (LPHD) is a B-cell lymphoproliferative disorder; patients with LPHD have an increased risk of developing synchronous or metachronous B-cell non-Hodgkin's lymphoma. The synchronous presence of LPHD and B-cell lymphoma in the same lymph node in some cases lends support to the argument that the B-cell lymphoma arises as a consequence of transformation or progression of LPHD. We have recently identified three cases of LPHD occurring simultaneously with T-cell lymphoma in a series of 76 cases of LPHD in the files of the Nebraska Lymphoma Study Group Registry. In large areas of the lymph nodes, atypical T cells with large, irregular, and hyperchromatic nuclei were admixed with Reed-Sternberg variants characteristic of LPHD (L&H cells). However, in all cases, areas of typical nodular LPHD without obvious T-cell lymphoma were also evident. In one case, frozen-section immunohistochemistry demonstrated the absence of expression of CD5, CD4, or CD8 by the T-cell lymphoma. The L&H cells in all cases expressed CD45 and CD20, as expected. In all three cases, clonal T-cell receptor (TCR)-gamma gene and TCR-beta gene rearrangements were documented by polymerase chain reaction analysis and Southern blotting, respectively. No clonally rearranged immunoglobulin genes were detected by either technique. To our knowledge, this represents the first report of the simultaneous occurrence of LPHD and T-cell lymphoma. Although B-cell lymphoma occurring in the setting of LPHD is a well-recognized phenomenon, previous reports of T-cell lymphoma occurring after a diagnosis of LPHD, as well as our cases with synchronous disease, suggest that the association of T-cell lymphoma and LPHD may not be uncommon as well. Furthermore, our cases indicate that T-cell lymphoma occurring in LPHD is not therapy related. However, the underlying mechanisms by which these composite lymphomas occur remain unknown.
 ...
PMID:Concurrent lymphocyte predominance Hodgkin's disease and T-cell lymphoma. A report of three cases. 877 90

The Epstein-Barr virus (EBV) latency C promoter drives expression of a family of viral proteins commonly targeted by CD8 cytotoxic T cells. These proteins are not generally expressed in African Burkitt's lymphoma and in EBV-associated Hodgkin's disease. The failure to express these proteins is almost certainly an important factor in the evasion of immunosurveillance by EBV-associated tumors. In a previous study, we have shown that transcriptional activation of the C promoter is inhibited by methylation of a particular CpG site upstream of the promoter that prevents binding of a cellular protein (CBF2), and we have shown that this and adjacent CpG sites are methylated in a Burkitt's lymphoma cell line. In the present study, we show that CpG sites in the CBF2 binding region are predominantly methylated in African Burkitt's lymphoma and in EBV-associated Hodgkin's disease. In addition, we present the first direct evidence that the C promoter is transcriptionally silent in Burkitt's lymphoma. In contrast, we show a complete absence of methylation in the CBF2 binding region in a case of reversible EBV-associated B-cell lymphoma arising in an immunocompromised patient whose tumor shows C promoter transcriptional activity. By inhibiting expression of highly antigenic viral proteins, methylation of transcriptional control sequences may veil the presence of virus in tumor tissue from CD8(+) cytotoxic T-cell immune surveillance and thus facilitate viral tumorigenesis.
 ...
PMID:CpG methylation of the major Epstein-Barr virus latency promoter in Burkitt's lymphoma and Hodgkin's disease. 887 13

T-cell non-Hodgkin's lymphomas are an uncommon occurrence after solid-organ transplantation. We describe a morphologically and immunophenotypically distinct group of T-cell lymphoproliferative disorders that occurred late in the course of six patients with solid-organ transplants. The patients ranged in age from 31 to 56 years (median, 43). Three were male; all were splenectomized. The interval from transplant to the diagnosis of lymphoma ranged from 4 to 26 years (median, 15). Symptoms at presentation were related to sites of involvement. Pulmonary, marrow, and CNS involvement were present in five, four, and one case, respectively. No patient had lymphadenopathy. Five patients had an elevated lactate dehydrogenase level (range, 226 to 4,880 IU/L; median, 1,220 IU/L). Five of six patients had a leukoerythroblastic reaction. All cases had large-cell histology and frequently contained cytoplasmic granules. Those cases tested expressed CD2, CD3, and CD8 and were negative for B-cell antigens. T-cell receptor beta- and gamma-chain genes were clonally rearranged in three of three and one of three cases, respectively. All T-cell posttransplant lymphoproliferative disorders (T-PTLDs) studied were negative for Epstein-Barr virus (EBV), human T-cell leukemia/lymphoma virus type 1 (HTLV-1), human T-cell leukemia/lymphoma virus type 2 (HTLV-2), and human herpes virus type 8 (HHV-8) genomes. Treatment with acyclovir (three patients) or chemotherapy (three patients) resulted in two responses. All patients had an aggressive course, with a median survival duration of 5 weeks. In conclusion, a clinically aggressive T-PTLD may be a late complication of solid-organ transplantation and does not appear to be related to EBV, HTLV-1, HTLV-2, or HHV-8 infection.
 ...
PMID:Posttransplant T-cell lymphoproliferative disorders--an aggressive, late complication of solid-organ transplantation. 912 60

Hodgkin's disease is characterized by an immune response in the involved tissues that is predominantly CD4 mediated. The CD4+ T-cells are CD45RO+ and CD45RBdim, they express several activation markers but lack CD26, and in vitro can be stimulated to produce gamma-interferon and IL-4, but not IL-2. This is not the usual immunophenotype and cytokine production pattern of Th1, Th2 or Th0 cells and may be a reflection of anergy. The cause of such an anergic reaction is not clear since RS cells express HLA class II as well as the co-stimulator molecules CD80 and CD86. It is possible that a (hypothetical) super antigen expressed on the RS cells may play a role. The absence of IL-2 production however explains the absence of a CD8 mediated response. In addition to that, RS cells generally do not express HLA class I, which allows them to escape CD8 mediated responses. The link between the ineffective immune response in the tissue and the generalized immune deficiency in Hodgkin's disease may consist of several components. These include the influx of mature T-cells into the affected tissues, the secretion of inhibitory molecules by the neoplastic cells and the spill-over of the anergic T-cell response into the general circulation by either the Hodgkin related antigen or also as a result of an IL-4 dominated response. The latter possibility may also be related to the hyper-gamma-globulinaemia and the frequently observed high IgE levels.
 ...
PMID:Immunology of Hodgkin's disease. 892 39

Clonality of T- and B-cell lymphoproliferative disorders can be determined by gene rearrangement studies when morphology and surface immunostaining are nondiagnostic. TcR and lg gene rearrangements have been demonstrated in many different hematologic disorders and TcR gene rearrangement has been particularly useful in the diagnosis of patients with CD8 large granular lymphocyte leukemias. TcR gene rearrangement may also be useful to distinguish Hodgkin's disease from T-cell non-Hodgkin's lymphoma. Gene rearrangement is usually performed by Southern analysis, and it is beneficial to run multiple enzyme-probe combinations to maximize the detection of clonal rearrangements. More recently, several laboratories have begun to use polymerase chain reaction (PCR) for gene rearrangement analysis. PCR offers an improved turnaround time, eliminates partial digestion artifacts, and allows for the use of paraffin embedded material. In addition to rearrangements of the TcR and lg genes, analysis of alterations in other genes such as bcl-1, bcl-2, bcl-6, and c-myc are also useful as clonal markers and aid in the classification of lymphomas.
 ...
PMID:Molecular genetics and lymphoproliferative disorders. 895 2

Six patients with human immunodeficiency virus (HIV)-associated non-Hodgkin lymphoma receiving chemotherapy (CT) with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) plus granulocyte colony-stimulating factor were sequentially monitored to study the effects of these treatments on their immunologic status (CD4 and CD8 cell counts) and on HIV plasma viremia. We show that mean CD4 cell counts declined significantly after the third cycle of CT (187 +/- 117/microliters before CT versus 92.4 +/- 60/microliters; p = 0.04) and remained significantly reduced 4 months after completion of CT. Modifications of CD8 cell counts were not statistically significant. The effects of CT on plasma viremia, as measured by a competitive polymerase chain reaction technique, were delayed until the fourth cycle, when an increase of viral load ranging from 0.6 to 2 logs (p = 0.027) was observed. After this point, viremia returned to baseline levels, with the exception of two patients who later developed opportunistic infections and one who underwent disease progression. These results suggest that, contrary to CD4 cell counts, plasma viremia could be a faithful surrogate marker for monitoring of HIV disease progression in patients undergoing CT.
 ...
PMID:The effects of antineoplastic chemotherapy on HIV disease. 895 47

Anaplastic large cell lymphoma (ALCL) is composed of large, frequently bizarre, cells of T- or null-cell phenotype that show a preferential sinusoidal growth pattern and consistent CD30 positivity. Whether these tumors represent a single entity or several, and what the exact cell origin, is controversial. Recently, granzyme B, a cytotoxic granule component, was reported in a small percentage of ALCL, suggesting that some cases may originate from cytotoxic lymphocytes. To further investigate this possibility, we performed an immunohistochemical study of 33 ALCLs of T- and null-cell type, using monoclonal antibodies to cytotoxic cell-associated antigens, including CD8, CD56, CD57, and the cytotoxic granular proteins perforin and TIA-1. In addition, CD4 expression was also evaluated. ALCL cases included 27 classical systemic forms and variants, 3 primary cutaneous (PC) forms, and 3 acquired immunodeficiency syndrome-associated forms. Cytotoxic antigen expression was also studied in 51 cases of Hodgkin's disease (HD) and 17 large B-cell lymphomas (LBCLs) with anaplastic cytomorphology and/ or CD30 positivity. We found that 76% of ALCLs, representing all subtypes except the PC forms, expressed either TIA-1, perforin, or both proteins. Expression of TIA-1 and perforin were highly correlated (P < .001). On the basis of their immunophenotypic profiles, several subtypes of cytotoxic antigen positive and negative ALCL could be recognized. Fifty-five percent of ALCLs (18 of 33) displayed an immunophenotypic profile consistent with cytotoxic T cells. Six cases expressed cytotoxic granular proteins in the absence of lineage specific markers, and one case expressed both T-cell- and natural killer cell-like markers. These 7 cases (21%) were placed into a phenotypic category of cytotoxic lymphocytes of unspecified subtype. Twenty-four percent (8 cases) of ALCLs were cytotoxic granule protein negative. All but one of these displayed a T-cell phenotype. Cytotoxic granule protein expression did not correlate with the presence of the NPM-ALK fusion transcript. Only 10% of the 51 HD cases were found to be TIA-1+, and none expressed perforin. Cytotoxic antigen expression was absent in LBCL. The expression of cytotoxic granule proteins in the majority of ALCL implies a cytotoxic lymphocyte phenotype and suggests that most cases originate from lymphocytes with cytotoxic potential. Furthermore, the demonstration of cytotoxic cell related proteins may be a useful addition to the current panel of antibodies used to distinguish ALCL, HD, and anaplastic LBCL.
 ...
PMID:Cytotoxic cell antigen expression in anaplastic large cell lymphomas of T- and null-cell type and Hodgkin's disease: evidence for distinct cellular origin. 902 30


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>